ATLA::Alternatives to Laboratory Animals

Volume 28, Number 4

A computer-based structure-activity relationship method for predicting the toxic effects of organic chemicals from one-dimensional representations of their molecular structures.

ATLA 28, 609-620, July/August 2000

Stephan Zinke and Ingrid Gerner

Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV), Department for the Assessment of Chemicals, Thielallee 88-92, 14195 Berlin, Germany

SUMMARY

A computer-based method is presented for the analysis and interpretation of structural formulae characterising chemical molecules. This method was developed to enable a computer to identify substructures of chemical molecules that are relevant in the context of specific toxicological questions. The new computer-based structure-examination method was used to develop the "structure" parts of several electronic structure-activity relationship models (SAR models) for analysing and interpreting the structural formula of a chemical from its one-dimensional representation, by applying recursive principles and identifying partial isomorphic graphs. The structure-examination method is designed as part of an open-endpoint procedure to be used in expert systems, and could be applied in the construction of SAR models for almost all toxicological endpoints. The system was satisfactorily tested by identifying substructures relevant to severely damaging effects on skin and eyes.

Keywords: analysis of structural formulae, modelling of structure-activity relationships, expert systems, prediction of local irritation/corrosion